Intrinsic frequency analysis for left ventricle ejection fraction or stroke volume determination

ABSTRACT

Hardware and software methodology are described for non-invasively monitoring cardiac health. Hemodynamic waveforms variously acquired for a subject are analyzed to calculate or approximate intrinsic frequencies in two domains in two domains across the Dicrotic Notch. Together with associated notch timing, heart rate and blood pressure values left ventricle ejection fraction and/or stroke volume can be determination.

RELATED APPLICATIONS

This filing is a continuation of U.S. patent application Ser. No.14/517,702, filed Oct. 17, 2014, which claims the benefit of andpriority to U.S. Provisional Patent Application Ser. Nos. 61/893,063,filed Oct. 18, 2013, and 62/003,735, filed May 28, 2014, all of whichare incorporated by reference herein in their entirety and for allpurposes.

FIELD

This filing relates to hemodynamic waveform analysis for left ventricleejection fraction and/or stroke volume determination.

BACKGROUND

Cardiovascular diseases (CVDs) are the underlying cause of about one ofevery three deaths in United States each year. Likewise, about 34% ofAmerican adults are suffering from one or more types of CVD. In 2010,the total direct and indirect cost of CVDs was approximately $503billion.

Certainly, there is an urgent need to develop new methods and devicesfor diagnosing and monitoring CVDs. Diagnosis enables early interventionand remediation. Monitoring may be a useful tool in behaviormodification and prediction, as well as in the avoidance of an acuteevent leading to emergency hospitalization, morbidity and/or mortality.New methods and devices to meet these and other needs advantageouslyemploy noninvasive measurement to reduce medical complications andincrease patient comfort. Ideally, they are also easy to use by medicalpersonnel and subjects themselves, especially in a home environment.

SUMMARY

Example embodiments of methods, systems, and devices based on IntrinsicFrequency (IF) concepts are described that enable measuring LeftVentricle Ejection Fraction (LVEF), Cardiac Output (CO), and StrokeVolume (SV) noninvasively. These embodiments consider the IntrinsicFrequencies associated with blood flow, in terms of its pressure wave,associated wall displacement wave, and/or flow wave, in order to performthe subject calculations. In many embodiments, only the shape of thewaves, without magnitude, are used for such calculations. Noninvasivemethods, systems and devices can also be used for measurements withoutthe requirement for calibration.

Other systems, devices, methods, features and advantages of the subjectmatter described herein will be or will become apparent to one withskill in the art upon examination of the following figures and detaileddescription. It is intended that all such additional systems, devices,methods, features and advantages be included within this description, bewithin the scope of the subject matter described herein, and beprotected by the accompanying claims. In no way should the features ofthe example embodiments be construed as limiting the appended claims,absent express recitation of those features in the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The figures provided herein may be diagrammatic and are not necessarilydrawn to scale, with some components and features exaggerated and/orabstracted for clarity. Variations from the embodiments pictured arecontemplated. Accordingly, depiction of aspects and elements in thefigures are not intended to limit the scope of the claims, except whensuch intent is explicitly stated therein.

FIGS. 1A and 1B diagrammatically illustrate the dynamic coupling of theheart and aorta in a human circulatory system.

FIGS. 2A and 2B are perspective views depicting example embodiments ofthe IF processing system.

FIG. 3 is a flowchart depicting an example embodiment of a method ofassessing IF parameters and performing a diagnosis.

FIG. 4A is a chart correlating measured Ejection Fraction and IntrinsicFrequency parameters.

FIG. 4B is a chart correlating measured ejection fraction and EjectionFraction calculated from Intrinsic Frequency.

FIGS. 5 and 6 are charts comparing Ejection Fraction calculated withhuman subjects from the 2D echocardiography versus Ejection Fractioncalculated with the subject IF methodology using skin motion waveform ata carotid artery location.

DETAILED DESCRIPTION

Before the present subject matter is described in detail, it is to beunderstood that this disclosure is not limited to the particularembodiments described, as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present disclosure will be limited onlyby the appended claims.

It should be noted that all features, elements, components, functions,and steps described with respect to any embodiment provided herein areintended to be freely combinable and substitutable with those from anyother embodiment. If a certain feature, element, component, function, orstep is described with respect to only one embodiment, then it should beunderstood that that feature, element, component, function, or step canbe used with every other embodiment described herein unless explicitlystated otherwise. This paragraph therefore serves as antecedent basisand written support for the introduction of claims, at any time, thatcombine features, elements, components, functions, and steps fromdifferent embodiments, or that substitute features, elements,components, functions, and steps from one embodiment with those ofanother, even if the following description does not explicitly state, ina particular instance, that such combinations or substitutions arepossible. It is acknowledged that express recitation of every possiblecombination and substitution is overly burdensome, especially given thatthe permissibility of each and every such combination and substitutionwill be readily recognized by those of ordinary skill in the art.

As explained in USPPN 2013/0184573, pressure and flow waves generated bythe heart propagate in the compliant arterial vasculature. FIG. 1Aillustrates a coupled heart-aorta system 10 in systole, with the aorticvalve open (not shown) and blood being pumped by the heart 12 into theaorta 14. As such, the heart and aorta construct a coupled dynamicsystem before the closure of the aortic valve. As shown in FIG. 1B,after the valve closure during diastole, the heart and aorta systems aredecoupled in a second system state 10′.

The aortic waves in each state include information about heart dynamics,arterial network dynamic and heart-aorta coupling. Extraction of suchinformation by analysis as described in further detail herein is basedon Intrinsic Frequency (IF) methodology enabling the calculation orapproximation of:

-   -   Left Ventricle Ejection Fraction (LVEF) from an arterial        pressure waveform alone;    -   left ventricle Stroke Volume (SV) of the heart from such a        pressure waveform alone;    -   Cardiac Output (CO) of the heart from such a pressure waveform        alone;    -   Left Ventricle Ejection Fraction (LVEF) from an arterial wall        displacement waveform alone;    -   left ventricle Stroke Volume (SV) from such a wall displacement        waveform alone; and/or    -   Cardiac Output (CO) from such a wall displacement waveform        alone.        Notably, traditional methods of data analysis are based on the        assumption of that the data will be stationary and linear.        Fourier analysis is just a typical, and often used, method.        However, it is a known fact that the stationariness and        linearity assumptions do not hold for arterial waves.        Accordingly, a new method of Sparse Time-Frequency        Representation (STFR) has been developed that may be applied        herein to achieve the above, and still other methods and goals.

The STFR method is employed because it is well suited for nonlinear dataanalysis, it is less sensitive to noise perturbation and, it preservessome intrinsic physical property of the signal. The general STFR problemis defined as follows:

$\begin{matrix}{{{Minimize}\mspace{31mu} M}{{{{Subject}\mspace{14mu} {to}\text{:}\mspace{14mu} {s(t)}} = {\sum_{i = 1}^{M}{{a_{i}(t)}\cos \; {\theta_{i}(t)}}}},{{{a_{i}(t)}\cos \; {\theta_{i}(t)}} \in D},\left( {{i = 1},\ldots \mspace{11mu},M} \right)}} & (1)\end{matrix}$

In the embodiments described herein a simplified and modified version ofSTFR may be employed by minimizing:

$\begin{matrix}{{\begin{matrix}{{f(t)} - {a_{1}{X\left( {0,T_{0}} \right)}{Cos}\; \omega_{1}t} - {b_{1}{X\left( {0,T_{0}} \right)}{Sin}\; \omega_{1}t} -} \\{{a_{2}{X\left( {T_{0},T} \right)}{Cos}\; \omega_{2}t} - {b_{2}{X\left( {T_{0},T} \right)}{Sin}\; \omega_{2}t} - c}\end{matrix}}_{2}^{2}{X\left( {a,b} \right)} = \left\{ {\begin{matrix}1 & {a \leq t \leq b} \\0 & {otherwise}\end{matrix}{Subject}\mspace{14mu} {to}\text{:}\mspace{14mu} \left\{ \begin{matrix}{{{a_{1}{Cos}\; \omega_{1}T_{0}} + {b_{1}{Sin}\; \omega_{1}T_{0}}} = {{a_{2}{Cos}\; \omega_{2}T_{0}} + {b_{2}{Sin}\; \omega_{2}T_{0}}}} \\{a_{1} = {{a_{2}{Cos}\; \omega_{2}T} + {b_{2}{Sin}\; \omega_{2}T}}}\end{matrix} \right.} \right.} & (2)\end{matrix}$

where, T₀ is the time of aortic valve closure (i.e., at a measured orcharted Dicrotic Notch in a hemodynamic waveform) in order to determineIF ω₁, ω₂ values and other IF parameters such as a₁, b₁, a₂, b₂, and cconstants fit to the waveform in the two domains on either side of theDicrotic Notch. Further details regarding IF parameter determination aredescribed in USPPN 2013/0184573, which is incorporated by reference inits entirety for all purposes.

LVEF and/or SV can be determined as shown in equations 3 and 4:

LVEF=f ₁(IFs, p _(min) , p _(max) , p _(mean) , T ₀, HR)   (3)

SV=f ₂(IFs, p _(min) , p _(max) , p _(mean) , T ₀, HR)   (4)

where IFs are the intrinsic frequency parameters (ω₁, ω₂, a₁, b₁, a₂,b₂, and c), p_(min) is the minimum of the hemodynamic waveform signal(which, as will be understood by those of ordinary skill in the art, canbe measured with a device that outputs a signal, for example, in termsof voltage, light intensity, microwave intensity, other wave intensity,displacement, or pressure) in the cardiac cycle corresponding todiastolic pressure, p_(max) is the maximum of the signal (which againcan be in terms of voltage, pressure, etc. per above) in the cardiaccycle corresponding to systolic pressure, p_(mean) is the mean of thesignal (again, in terms of voltage, pressure, etc.) over the wholecardiac cycle, T₀ is left ventricle ejection time or the notch time(i.e., time from the onset of the waveform to notch), and HR is theheart rate. Cardiac Output (CO) can be calculated by multiplying SV andHR.

The combination of parameters used in these formulas depends on thelocation where the waveform is measured and the nature of the waveformobtained (e.g., as between a pressure wave, vessel wall displacementwave and skin motion wave). As empirically determined, in the case ofusing ascending aortic pressure waveforms, f₁ and f₂ in equations 3 and4 become expressions as in equation 5 and 6 below, respectively. Assuch, LVEF and/or SV can be calculated using the equations:

$\begin{matrix}{{LVEF} = {k_{1} - {{k_{2}\left( \frac{SR}{1 - {SR}} \right)}C_{R}\frac{\omega_{1}}{\omega_{2}}}}} & (5) \\{{SV} = {k_{3}\left( {\omega_{2} - {{k_{4}\left( \frac{SR}{1 - {SR}} \right)}C_{R}\omega_{1}}} \right)}} & (6)\end{matrix}$

where SR is the systolic time ratio (SR=T₀/HR) and k₁, k₂, k₃, and k₄are universal constants. C_(R) can be calculated using the followingequation:

$\begin{matrix}{C_{R} = \frac{c - p_{\min}}{p_{\max} - p_{\min}}} & (7)\end{matrix}$

These waveforms employed can be acquired and/or processed using systemsas illustrated in FIGS. 2A and 2B. Waveforms captured and/or IF resultsbased on the same may be produced and/or displayed in real time forphysician evaluation and/or logged for monitoring or subsequentevaluation of a physician or other analysis. Alternatively, diagnosisbased on the IF results may be displayed, alarms may be triggered, andso forth, for users who are not either medically or specially trained(e.g., as in the case of home use or general practice physicians).

Regardless, what is meant by “real time” in the context above willgenerally mean that it takes about 1 second or less from the time ofdata acquisition for calculation and data presentation. Ideally, suchaction occurs or is performed without perceptible delay. However stated,real time activity in the subject embodiments concerns manipulation ofsuch a mass of data and calculations that the task is well beyondpracticable human capacity, thereby requiring the use of a computerprocessor.

In any case, FIG. 2A diagrammatically illustrates a computer-basedsystem 100 in which a scanner 110 includes on-board electronics forsending and receiving signals 112 to acquire hemodynamic waveformmeasurements. Use of microwave sensor (at least for measuring vesseldisplacement) and/or ultrasound sensors (for measuring either or both ofvessel distension and blood velocity/flow) for such purposes is wellknown. An example of suitable publicly-available hardware includes thatemployed in the GE LOGIQ Book Portable Ultrasound Machine, whichtechnology is readily adapted to the subject methods and systems.Suitable microwave sensor technology is described in Fletcher, R R, andS Kulkarni, “Clip-on wireless wearable microwave sensor for ambulatorycardiac monitoring,” IEEE, 2010. 365-369. Web. 3 Feb. 2012.

Other types of scanners may be used as well. These include tonomeric andoptical units. In the former case, the tonomeric sensor will include aforce or pressure sensing transducer producing an electronic signal(e.g., voltage output) corresponding to a pressure or wall-displacementbased hemodynamic waveform. The optical scanner may embody any of avariety of technologies in producing a signal that correlates to ahemodynamic waveform. In one embodiment, the optical scanner may includeinfrared (IR) diode(s) and sensor(s) suitable for measuring a walldisplacement waveform. In another embodiment, the scanner operates as acamera. In which case (whether in a flat-bed scanner format, in typicalstand-alone digital camera format, or incorporated in the bezel of aiPAD or the like), such a device is able to capture a printed orotherwise displayed hemodynamic waveform and convert it to a digitalrepresentation employing a CCD, CMOS or the like. Then, a computerprogram such as the UN-SCAN-IT Graph Digitizer can be employed toproduce a signal representative of the captured hemodynamic waveform tobe received by a computer processor for analysis.

Accordingly, scanner 110 may be hand-held for scanning a seated orstanding patient 90 as shown. Or the scanner hardware may beincorporated in a C-arm or tunnel for scanning a patent lying down.Other scanner hardware options are presented in U.S. Pat. Nos. 5,363,855and 5,439,001, both of which are incorporated herein by reference intheir entirety for all purposes, as well as the incorporated USPPN2013/0184573 document.

A hand-held scanner may advantageously be battery-powered so as to avoidconnection to a wall socket. Whether hand-held or incorporated or in alarger unit, scanner 110 may interface by wireless (as indicated) orwired (not shown) communication with a general purpose computer 120,optionally including display 122 to perform and communicate results,respectively. Otherwise, on-board processing and/or display hardware maybe provided in connection with the sensor housing itself. Such optionsmay be especially useful for a hand-held or semi-portable device asthese may be used by a patient/subject at home, during travel, etc.

Notably, all the hardware may be located in one location. Alternatively,the computer system may be located at a remote location as in a “Cloud”based option. Further, the system may consist of the computer and itsprogramming without a sensor means. In such a case, the system mayinclude an optical scanner or other camera means for image or otherelectronic capture of a waveform produced by another (already available)measurement machine (e.g., the aforementioned GE scanner, etc.).

As yet another option, FIG. 2B, illustrates a portable system 100′. Itincludes a tablet-style computer device 124 (e.g., an iPAD) with anintegral display 122. A tonomeric or optical scanner 110′ is shownconnected to computer 124 via a bus 126 and wired connection 128.However, the scanner (of whatever type) may be wirelessly connected asin the previous example as well. Alternatively, the scanner employed incapturing the hemodynamic waveform may be the camera 110″ integrated inthe device.

Regardless of how the hemodynamic waveform(s) is/are acquired, a givenwaveform can be analyzed as described in the embodiment of FIG. 3.Specifically, in method 200 one or more waveforms are obtained foranalysis at 202. The data may originally be in digital form or convertedthereto. It may come from a pressure wave, wall displacement wave and/orflow wave. However obtained, at 204, IF parameters can be calculated perEquation (2).

At 206, Left Ventricle Ejection Fraction (LVEF) may be calculated. Fromthis, at 208, diagnosis may be made regarding cardiovascular disease(CVD) together with an assessment of associated risk. Doing so based onejection fraction values is something within the common capabilities ofphysicians. Such diagnosis and/or assessment may instead bycomputerized. Likewise, assigning or recommending an appropriate therapyor prevention strategy may be offered at 214 by a physician or promptedby look-up and output from a computer database.

In addition to or as an alternative to LVEF calculation, the subjectsystem may calculate Stroke Volume (SV) as at 210. Once obtained,cardiac output (CO) can be calculated at 212 as the product of SV and asubject's heart rate. Diagnosis/assessment (as at 208) may follow as mayrecommended therapy/prevention activity (as at 214).

EXAMPLES

FIG. 4A presents a chart 220 demonstrating the correlation betweeninvasively measured and IF parameters (ω1 and ω2) calculated usingequation (5). Here, pressure and echocardiogram data are from samplingwith three dogs. Pressure was measured invasively and EF was measured byechocardiogram. In the chart, EF measured by 2D echocardiographymethodology is presented (y-axis, EF-echo) versus the IF parameterscalculated via equation 5 (x-axis, f (ω1 and ω2) employing invasiveascending aortic pressure waveforms that were measured simultaneouslywith the 2D echo procedure. The two dashed lines are ±10% error lines.(Notably, EF-echo by itself inherently includes 15% error.) As such,chart 220 indicates excellent agreement between direct EF measurementand those derived by IF method in calculation of EF from waveforminformation.

In FIG. 4B, chart 220′ illustrates a related comparison with six dogs.As above, IF methodology was employed using a modified version of SparseTime-Frequency Representation (STFR) to extract the IntrinsicFrequencies (ω1 and ω2) from the pressure wave measured invasively inthe dogs. As shown, LVEF calculated from IF is presented along thex-axis of the graph as compared to LVEF measured by standardechocardiography (EF-echo). Again, the results demonstrate a strongagreement between the EF-echo and the ejection fractions approximatedfrom the IF parameters. The dotted lines represent ±15% error lines.Most importantly, all low ejection fraction data points (<40%) arewithin the error boundary.

The intrinsic frequencies can also be extracted from measurement of themotion of the skin in locations where an artery is passing underneaththe skin such as at the neck (carotid location), arm (brachial location)and wrist (radial location). In FIG. 5, chart 230 shows ejectionfraction calculated from the 2D echocardiography (EF-echo) versus EFcalculated from the IF method (EF-IF) using skin motion waveform at theneck (carotid artery location) of human test subjects. The skin motionwaveforms were measured using a smart phone camera and light. Again,equation 5 was used to calculate EF with k1 and k2 both about equal to 1offering optional solution. The dotted lines in the chart are 15% errorlines. Again, excellent agreement between the echo- and IF-based isdemonstrated. Other functions might be used in the alternative afterfurther study.

For the same measurements and calculations represented in FIG. 5, FIG. 6provides a Bland Altman plot 240 showing the agreement between theclinically established EF-echo method and the subject EF-IF method fromskin wave motion. As evident, there is no evidence of any particularproportional or magnitude related error. Rather, an overall systemicvariability is noted that is consistent with the above-referenced errorin echocardiography EF measurement.

Variations

In addition to the embodiments that been disclosed in detail above,still more are possible within the classes described and the inventorsintend these to be encompassed within this Specification and claims.This disclosure is intended to be exemplary, and the claims are intendedto cover any modification or alternative which might be predictable to aperson having ordinary skill in the art.

Moreover, the various illustrative processes described in connectionwith the embodiments herein may be implemented or performed with ageneral purpose processor, a Digital Signal Processor (DSP), anApplication Specific Integrated Circuit (ASIC), a Field ProgrammableGate Array (FPGA) or other programmable logic device (PLD), discretegate or transistor logic, discrete hardware components, or anycombination thereof designed to perform the functions described herein.A general purpose processor may be a microprocessor, but in thealternative, the processor may be any conventional processor,controller, microcontroller, or state machine. The processor can be partof a computer system that also has a user interface port thatcommunicates with a user interface, and which receives commands enteredby a user, has at least one memory (e.g., hard drive or other comparablestorage, and random access memory) that stores electronic informationincluding a program that operates under control of the processor andwith communication via the user interface port, and a video output thatproduces its output via any kind of video output format, e.g., VGA, DVI,HDMI, DisplayPort, or any other form.

A processor may also be implemented as a combination of computingdevices, e.g., a combination of a DSP and a microprocessor, a pluralityof microprocessors, one or more microprocessors in conjunction with aDSP core, or any other such configuration. These devices may also beused to select values for devices as described herein. The camera may bea digital camera of any type including those using CMOS, CCD or otherdigital image capture technology.

The steps of a method or algorithm described in connection with theembodiments disclosed herein may be embodied directly in hardware, in asoftware module executed by a processor, or in a combination of the two.A software module may reside in Random Access Memory (RAM), flashmemory, Read Only Memory (ROM), Electrically Programmable ROM (EPROM),Electrically Erasable Programmable ROM (EEPROM), registers, hard disk, aremovable disk, a CD-ROM, or any other form of storage medium known inthe art. An exemplary storage medium is coupled to the processor suchthat the processor can read information from, and write information to,the storage medium. In the alternative, the storage medium may beintegral to the processor. The processor and the storage medium mayreside in an ASIC. The ASIC may reside in a user terminal. In thealternative, the processor and the storage medium may reside as discretecomponents in a user terminal.

In one or more exemplary embodiments, the functions described may beimplemented in hardware, software, firmware, or any combination thereof.If implemented in software, the functions may be stored on, transmittedover or resulting analysis/calculation data output as one or moreinstructions, code or other information on a computer-readable medium.Computer-readable media includes both computer storage media andcommunication media including any medium that facilitates transfer of acomputer program from one place to another. A storage media may be anyavailable media that can be accessed by a computer. By way of example,and not limitation, such computer-readable media can comprise RAM, ROM,EEPROM, CD-ROM or other optical disk storage, magnetic disk storage orother magnetic storage devices, or any other medium that can be used tocarry or store desired program code in the form of instructions or datastructures and that can be accessed by a computer. The memory storagecan also be rotating magnetic hard disk drives, optical disk drives, orflash memory based storage drives or other such solid state, magnetic,or optical storage devices. Also, any connection is properly termed acomputer-readable medium. For example, if the software is transmittedfrom a website, server, or other remote source using a coaxial cable,fiber optic cable, twisted pair, digital subscriber line (DSL), orwireless technologies such as infrared, radio, and microwave, then thecoaxial cable, fiber optic cable, twisted pair, DSL, or wirelesstechnologies such as infrared, radio, and microwave are included in thedefinition of medium. Disk and disc, as used herein, includes compactdisc (CD), laser disc, optical disc, digital versatile disc (DVD),floppy disk and Blu-ray disc where disks usually reproduce datamagnetically, while discs reproduce data optically with lasers.Combinations of the above should also be included within the scope ofcomputer-readable media.

Operations as described herein can be carried out on or over a website.The website can be operated on a server computer, or operated locally,e.g., by being downloaded to the client computer, or operated via aserver farm. The website can be accessed over a mobile phone or a PDA,or on any other client. The website can use HTML code in any form, e.g.,MHTML, or XML, and via any form such as cascading style sheets (“CSS”)or other.

Also, the inventors intend that only those claims which use the words“means for” are intended to be interpreted under 35 USC 112, sixthparagraph. Moreover, no limitations from the specification are intendedto be read into any claims, unless those limitations are expresslyincluded in the claims. The computers described herein may be any kindof computer, either general purpose, or some specific purpose computersuch as a workstation. The programs may be written in C, or Java, Brewor any other programming language. The programs may be resident on astorage medium, e.g., magnetic or optical, e.g. the computer hard drive,a removable disk or media such as a memory stick or SD media, or otherremovable medium. The programs may also be run over a network, forexample, with a server or other machine sending signals to the localmachine, which allows the local machine to carry out the operationsdescribed herein.

Also, it is contemplated that any optional feature of the embodimentvariations described may be set forth and claimed independently, or incombination with any one or more of the features described herein.Reference to a singular item, includes the possibility that there is aplurality of the same items present. More specifically, as used hereinand in the appended claims, the singular forms “a,” “an,” “said,” and“the” include plural referents unless specifically stated otherwise. Inother words, use of the articles allow for “at least one” of the subjectitem in the description above as well as the claims below. It is furthernoted that the claims may be drafted to exclude any optional element. Assuch, this statement is intended to serve as antecedent basis for use ofsuch exclusive terminology as “solely,” “only” and the like inconnection with the recitation of claim elements, or use of a “negative”limitation.

Without the use of such exclusive terminology, the term “comprising” inthe claims shall allow for the inclusion of any additional elementirrespective of whether a given number of elements are enumerated in theclaim, or the addition of a feature could be regarded as transformingthe nature of an element set forth in the claims. Except as specificallydefined herein, all technical and scientific terms used herein are to begiven as broad a commonly understood meaning as possible whilemaintaining claim validity.

While the embodiments are susceptible to various modifications andalternative forms, specific examples thereof have been shown in thedrawings and are herein described in detail. It should be understood,however, that these embodiments are not to be limited to the particularform disclosed, but to the contrary, these embodiments are to cover allmodifications, equivalents, and alternatives falling within the spiritof the disclosure. Furthermore, any features, functions, steps, orelements of the embodiments may be recited in or added to the claims, aswell as negative limitations that define the inventive scope of theclaims by features, functions, steps, or elements that are not withinthat scope.

What is claimed is:
 1. A system for acquiring and analyzing ahemodynamic waveform of a subject by Intrinsic Frequency (IF) analysis,the system comprising: a scanner adapted to capture a signalcorresponding to a hemodynamic waveform; and at least one computerprocessor connected to the scanner by a wired or wireless connection,wherein the computer processor is adapted to receive the signal for thehemodynamic waveform, determine a Dicrotic Notch using the signal,calculate first and second intrinsic frequencies (ω₁, ω₂) on each sideof the Dicrotic Notch and at least one of other IF parameters includinga₁, b₁, a₂, b₂, and c for the waveform, and output a signalcorresponding to at least one of left ventricle ejection fraction (LVEF)and stroke volume (SV).
 2. The system of claim 1, wherein LVEF iscalculated as a function of the IF parameters and p_(min), p_(max),p_(mean), T₀ and HR.
 3. The system of claim 1, wherein SV is calculatedas a function of the IF parameters and p_(min), p_(max), p_(mean), T₀and HR.
 4. A computer readable medium having stored thereoninstructions, which when executed cause one or more processors to:determine a Dicrotic Notch using an input signal corresponding to ahemodynamic waveform; calculate, by Intrinsic Frequency (IF) analysis,first and second intrinsic frequencies (ω₁, ω₂) on each side of theDicrotic Notch and at least one of other IF parameters including a₁, b₁,a₂, b₂, c for the hemodynamic waveform; and output a signalcorresponding to at least one of left ventricle ejection fraction (LVEF)and stroke volume (SV).
 5. The computer readable medium of claim 4,including instructions for LVEF calculation as a function of the IFparameters and p_(min), p_(max), p_(mean), T₀ and HR.
 6. The computerreadable medium of claim 4, including instructions for SV calculation asa function of the IF parameter and p_(min), p_(max), p_(mean), T₀ andHR.
 7. A method of analyzing a signal using a computer comprising aprocessor, the method comprising: noninvasively acquiring a signal for ahemodynamic waveform of a subject with a sensor device, wherein thesignal is acquired without calibrating the sensor device, and whereinthe sensor device outputs signal magnitude by a selection of voltage,light intensity, microwave intensity, displacement or pressure;analyzing, by the processor, the signal magnitude of each of a firstsection and a second section of the hemodynamic waveform signal, whereinthe waveform includes a Dicrotic Notch, to determine first and secondintrinsic frequencies (ω1, ω2) on opposite sides of the Dicrotic Notch;and outputting, by the processor, a result for at least one of leftventricle ejection fraction (LVEF) and stroke volume (SV).
 8. The methodof claim 7, wherein LFEF is calculated as a function of at least some ofIntrinsic Frequency parameter (ω₁, ω₂, a₁, b₁, a₂, b₂, c) and p_(min),p_(max), p_(mean), T₀ and HR.
 9. The method of claim 7, wherein SV iscalculated as a function of at least some of Intrinsic Frequencyparameter (ω₁, ω₂, a₁, b₁, a₂, b₂, c) and p_(min), p_(max), p_(mean), T₀and HR.
 10. The method of claim 7, wherein the waveform is selected froman arterial pressure wave, a wall displacement wave, a flow wave, or avelocity wave.
 11. The method of claim 10, wherein the waveform isobtained from skin motion.